Sleeping pills owe half their benefits to placebo effect, study finds

Half of the benefit of taking sleeping pills comes from the placebo effect, according to a major new study published in the British Medical Journal.

20 dec 2012--Researchers re-analysed results from more than a dozen clinical trials of the most common type of sleeping tablets, known as Z-drugs (non-benzodiazepine hypnotics).

These drugs are frequently used in the UK and USA as a short-term treatment for insomnia with almost £25m worth of prescriptions handed out in Britain each year. However, some health experts have questioned whether the benefits of Z-drugs justify their side effects, which can include memory loss, fatigue and impaired balance.

Questions have also been raised about the validity of published research into the effects of these drugs based on trials sponsored by pharmaceutical companies themselves.

Academics from the University of Lincoln, Harvard Medical School and University of Connecticut conducted a meta-analysis of data from clinical trials of Z-drugs comparing drug effects with placebo effects. This type of comparison enables researchers to determine how much of the drug effect comes from the constituents of the drug itself, and how much is due to other factors (like the placebo response or regression to the mean).

They used data submitted by pharmaceutical companies to the US Food and Drug Administration (FDA) for approval of new products. This included 13 clinical trials containing 65 different comparisons and more than 4,300 participants.

The FDA collates results from both published and unpublished studies, enabling researchers to avoid common types of bias (such as reporting bias) which can undermine other research based on sponsored trials.

Their findings, published in this week's British Medical Journal, indicate that once the placebo effect is discounted, the drug effect is of 'questionable clinical importance'.

Lead author Professor Niroshan Siriwardena, from the School of Health and Social Care at the University of Lincoln, said: "Our analysis showed that Z-drugs did reduce the length of time it took for subjects to fall asleep, both subjectively and as measured in a sleep lab, but around half of the effect of the drug was a placebo response.

"There was not enough evidence from the trials to show other benefits that might be important to people with sleep problems, such as sleep quality or daytime functioning.

"We know from other studies that around a fifth of people experience side effects from sleeping tablets and one in one hundred older people will have a fall, fracture or road traffic accident after using them.

"Psychological treatments for insomnia can work as effectively as sleeping tablets in the short-term and better in the long-term, so we should pay more attention to increasing access to these treatments for patients who might benefit."

He said future studies of sleeping tablets should investigate a broader range of outcomes, not just time taken to fall asleep, and that pharmaceutical companies should be more transparent in disclosing results from their studies so that researchers can independently analyse their results.

The paper 'Effectiveness of non-benzodiazepine hypnotics in the treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration' was published in the British Medical Journal on 17th December 2012.

More information: 'Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration'; Tania B Huedo-Medina, Irving Kirsch, Jo Middlemass, Markos Klonizakis, A Niroshan Siriwardena; BMJ 2012; 345 doi: dx.doi.org/10.1136/bmj.e8343 (Published 17 December 2012)

Provided by University of Lincoln

Inpatient sleeping drug quadrupled fall risk

A drug commonly prescribed to help patients sleep in hospitals has been associated with an increased risk of falls, according to a study published in the Journal of Hospital Medicine.

23 nov 2012--U.S. sleep specialists from the Mayo Clinic found that the fall rate among the 4,962 patients who took zolpidem during their hospital stay was more than four times as high as the 11,358 who did not take the drug.

They also found that the risk posed by the drug was greater than the risks posed by factors such as age, cognitive impairment, delirium or insomnia, regardless of the dosage used.

"Ensuring that people get enough sleep during their hospital stay is very important, but it can also prove very challenging," says the Clinic's Chief Patient Safety Officer Dr. Timothy I. Morgenthaler, who specializes in sleep disorders and pulmonary and critical care.

"Patient falls are also a significant patient safety issue in hospitals and one that has been quite difficult to tackle, despite considerable efforts. That is why it is one of the target aims of the U.S. Department of Health and Human Services Partnership for Patients project."

"Discovering that zolpidem, which is commonly used in hospitals, is a significant risk factor for patient falls provides us with additional knowledge to help tackle this problem."

Key findings of the study include: 

• Just under 39 percent of eligible admissions during 2010 were prescribed zolpidem (16,320 patients) but 88 percent of the prescriptions were issued on an "as needed basis."
• Zolpidem was administered to 30.4 percent of patients who were prescribed it and to 11.8 percent of all Mayo Clinic admissions in 2010.
• Just over three percent of the patients on zolpidem fell during their in-patient hospital stay, compared with 0.7 percent of the patients who did not take zolpidem.
• Zolipdem use continued to be associated with an increased fall risk when other key factors, including health, length of hospital stay and assessed fall risk, were taken into consideration.

"Our hospitals have an overall fall rate of about 2.5 per 1000 patient days, which is lower than many national benchmarks. However, we have not been able to significantly reduce this rate in recent years. Now, we calculate that for every 55 patients who received zolpidem, there was one additional fall that may have been avoided by not administering the drug," says Dr. Morgenthaler.

"As a result of our study, we are now phasing out zolpidem and moving toward sleep enhancement techniques that are not based on drugs and which we believe are safer and probably as effective."

More information: Morgenthaler et al. Zolpidem is Independently Associated with Increased Risk of Inpatient Falls. Journal of Hospital Medicine. DOI: 10.1002/jhm.1985

Provided by Wiley

Study finds higher death risk with sleeping pills

People are relying on sleeping pills more than ever to get a good night's rest, but a new study by Scripps Clinic researchers links the medications to a 4.6 times higher risk of death and a significant increase in cancer cases among regular pill users.

29 feb 2012--The results, published today by the open-access online journal BMJ Open, cast a shadow over a growing segment of the pharmaceutical industry that expanded by 23 percent in the United States from 2006 to 2010 and generated about $2 billion in annual sales.

"What our study shows is that sleeping pills are hazardous to your health and might cause death by contributing to the occurrence of cancer, heart disease and other ail-ments," said author Daniel F. Kripke, M.D., of the Viterbi Family Sleep Center in San Diego.

The research is the first to show that eight of the most commonly used hypnotic drugs were associated with increased hazards of mortality and cancer, including the popularly prescribed medications zolpidem (known by the brand name Ambien) and temazepam (also known as Restoril), Dr. Kripke said. Those drugs had been thought to be safer than older hypnotics because of their shorter duration of action.

Study participants who took sleeping pills were matched with control patients of similar ages, gender and health who received no hypnotics in order to eliminate the possibility that other factors led to the results.

"We tried every practical strategy to make these associations go away, thinking that they could be due to use by people with more health problems, but no matter what we did the associations with higher mortality held," said co-author Robert D. Langer, M.D., M.P.H., of the Jackson Hole Center for Preventive Medicine in Jackson, Wyoming.

Even among patients who were prescribed 1 to 18 sleeping pills per year, the risk of death was 3.6 times higher than among similar participants who did not take the medications. The study looked at patients aged 18 years and older, and found the increased risk in all age groups.

Rates of new cancers were 35 percent higher among patients who were prescribed at least 132 hypnotic doses a year as compared with those who did not take the drugs.

Using data stored in an electronic medical record that has been in place for more than a decade, the researchers obtained information on almost 40,000 patients cared for by a large integrated health system in the northeastern United States.

The study included 10,531 sleeping pill users who were prescribed the medications for an average of 2.5 years and 23,674 control participants who were not prescribed the drugs. Information came from outpatient clinic visits conducted between Jan. 1, 2002, and Sept. 30, 2006.

"It is important to note that our results are based on observational data, so even though we did everything we could to ensure their validity, it's still possible that other factors ex-plain the associations," said co-author Lawrence E. Kline, D.O., who is medical director of the Viterbi Family Sleep Center. "We hope our work will spur additional research in this area using information from other populations."

Funding for the study came from the Scripps Health Foundation and other philanthropic sources.

The BMJ Open report should prompt physicians to consider alternatives to hypnotic medications, Dr. Kline said.

Clinicians at the Viterbi Family Sleep Center focus on cognitive therapy that teaches patients to better understand the nature of sleep. For example, some people suffering from insomnia might require less than the eight hours of sleep commonly recommended for each night.

Patients also can benefit from practicing good sleeping habits and relaxation, as well as taking advantage of the body's natural clock, which is driven by the rising and setting of the sun, Dr. Kline said. "Understanding how to use the circadian rhythm is a very powerful tool that doesn't require a prescription," he said.

When insomnia results from emotional problems such as depression, doctors should treat the psychological disorder rather than prescribe sleeping pills that could prove to be harmful, Dr. Kripke said.

Provided by Scripps Health

Sleeping Pill Risks May Outweigh Benefits In Older Patients

TORONTO, Nov. 11-For insomnia patients 60 or older, the risk of dizziness or falls caused by sleeping pills may outweigh the benefits, according to a meta-analysis reported by investigators here.
Action Points
Consider alternatives to pharmacologic therapy for insomnia in older patients, such as cognitive behavioral therapy.In fact, older adults were more than twice as likely to suffer an adverse event as they were to experienced improved sleep, reported Usoa E. Busto, Pharm. D., of the Center for Addiction and Mental Health here in a study published online in the British Medical Journal.
However, this finding should be used as a "rough indicator only," as the meta-analysis included much more data on adverse events than on effectiveness, the study authors said.
The meta-analysis included 24 randomized, placebo-controlled studies done between 1996 and 2003. These studies included 2,417 participants 60 or older with insomnia but otherwise free of psychiatric or psychological disorders. In these studies, sleeping pills were taken for at least five and as many as 21 consecutive nights.
A total of 830 patients were treated with benzodiazepines, 106 with Imovane (zopiclone), 384 with Ambien (zolpidem), 609 with Sonata (zaleplon), 14 with the antihistamine diphenhydramine, and 468 with placebo.
The meta-analysis compared potential benefits (subjective reports of sleep variables) with cognitive adverse events (memory loss, confusion, disorientation); psychomotor adverse events (dizziness, loss of balance, falls); and residual morning sedation.
Overall, sleep quality improved 14% (P0.05), which the researchers calculated had a small effect size. Total sleep time improved by an average of about 25 minutes (P0.001), and the number of nighttime awakenings decreased by 63% (P0.001).
Adverse events were more common with sleep aids than placebo. Adverse cognitive events were 4.78 times more common (95% confidence interval=1.47-15.47; P0.01). Adverse psychomotor events were 2.61 times more common, although this did not reach statistical significance (95% CI=1.12-6.09; P >0.05). Residual daytime sedation was 3.82 times more common (95% CI=1.88-7.80; P0.001).
The researchers calculated that the number needed to treat for improved sleep quality was 13, while the number needed to harm for any adverse event was six. "This ratio indicates that an adverse event is more than twice as likely as enhanced quality of sleep," the study authors said.
"Although the improvements in sleep variables obtained from prescription sedative hypnotics are statistically significant, the effect size is small, and the clinical benefits may be modest at best," the researchers concluded.
"The added risk of an adverse event may not justify these benefits, particularly in a high risk elderly population. These factors should be considered when sedative hypnotics are prescribed for older patients," they advised.
Cognitive behavioral therapy has been shown to be as effective as pharmacotherapy for insomnia in older people, the investigators noted. Because fewer risks are associated with behavioral therapy, it may be a viable treatment alternative in a healthy elderly population with no cognitive impairment, the researchers suggested.
Some limitations of the study pointed out by the authors included the fact that "all sedatives or all benzodiazepines were grouped together for analyses, irrespective of differences in half life, potency, or dosage." Also, no standard method of collecting subjective sleep variables is available.Primary source: British Medical JournalSource reference: Glass J et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. British Medical Journal. Advanced online publication November 10, 2005.